tbuckley/cabot-search huggingface dataset:
Syk Activation in Circulating and Tissue Innate Immune Cells in Antineutrophil Cytoplasmic Antibody–Associated Vasculitis
Authors: Maria Prendecki, Kavita Gulati, Noelle Pisacano, Damilola Pinheiro, Tejal Bhatt, Marie‐Anne Mawhin, Frederic Toulza, Esteban S. Masuda, Andrew Cowburn, Katharine M. Lodge, Frederick W. K. Tam, Candice Roufosse, Charles D. Pusey, Stephen P. McAdoo
Journal: Arthritis & Rheumatology (2022)

Syk is a cytoplasmic protein tyrosine kinase that plays a role in signaling via B cell and Fc receptors (FcR). FcR engagement and signaling via Syk is thought to be important in antineutrophil cytoplasm antibody (ANCA) IgG-mediated neutrophil activation. This study was undertaken to investigate the role of Syk in ANCA-induced myeloid cell activation and vasculitis pathogenesis.Phosphorylation of Syk in myeloid cells from healthy controls and ANCA-associated vasculitis (AAV) patients was analyzed using flow cytometry. The effect of Syk inhibition on myeloperoxidase (MPO)-ANCA IgG activation of cells was investigated using functional assays (interleukin-8 and reactive oxygen species production) and targeted gene analysis with NanoString. Total and phosphorylated Syk at sites of tissue inflammation in patients with AAV was assessed using immunohistochemistry and RNAscope in situ hybridization.We identified increased phosphorylated Syk at critical activatory tyrosine residues in blood neutrophils and monocytes from patients with active AAV compared to patients with disease in remission or healthy controls. Syk was phosphorylated in vitro following MPO-ANCA IgG stimulation, and Syk inhibition was able to prevent ANCA-mediated cellular responses. Using targeted gene expression analysis, we identified up-regulation of FcR- and Syk-dependent signaling pathways following MPO-ANCA IgG stimulation. Finally, we showed that Syk is expressed and phosphorylated in tissue leukocytes at sites of organ inflammation in AAV.These findings indicate that Syk plays a critical role in MPO-ANCA IgG-induced myeloid cell responses and that Syk is activated in circulating immune cells and tissue immune cells in AAV; therefore, Syk inhibition may be a potential therapeutic option.
Should Low Serum Urate Be Exonerated? Untangling the Influence of Sarcopenia in Observational Studies
Authors: Kanon Jatuworapruk, Nicola Dalbeth
Journal: Arthritis & Rheumatology (2022)

Disclosure Form Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Target residence of Cas9-sgRNA influences DNA double-strand break repair pathway choices in CRISPR/Cas9 genome editing
Authors: Si-Cheng Liu, Yi-Li Feng, Xiu-Na Sun, Ruo-Dan Chen, Qian Liu, Jing-Jing Xiao, Jin-Na Zhang, Zhi-Cheng Huang, Ji-Feng Xiang, Guo-Qiao Chen, Yi Yang, Chao Lou, Hao-Dan Li, Zhen Cai, Shi-Ming Xu, Hui Lin, An-Yong Xie
Journal: Genome biology (2022)

Due to post-cleavage residence of the Cas9-sgRNA complex at its target, Cas9-induced DNA double-strand breaks (DSBs) have to be exposed to engage DSB repair pathways. Target interaction of Cas9-sgRNA determines its target binding affinity and modulates its post-cleavage target residence duration and exposure of Cas9-induced DSBs. This exposure, via different mechanisms, may initiate variable DNA damage responses, influencing DSB repair pathway choices and contributing to mutational heterogeneity in genome editing. However, this regulation of DSB repair pathway choices is poorly understood.
Drug hypersensitivity, in vitro tools, biomarkers, and burden with <scp>COVID</scp>‐19 vaccines
Authors: Francisca Palomares, Juan L. Paris, Marina Labella, Inmaculada Doña, Cristobalina Mayorga, María José Torres
Journal: Allergy (2022)

Hypersensitivity reactions to drugs are increasing worldwide. They display a large degree of variability in the immunological mechanisms involved, which impacts both disease severity and the optimal diagnostic procedure. Therefore, drug hypersensitivity diagnosis relies on both in vitro and in vivo assessments, although most of the methods are not well standardized. Moreover, several biomarkers can be used as valuable parameters for precision medicine that provide information on the endotypes, diagnosis, prognosis, and prediction of drug hypersensitivity development, as well on the identification of therapeutic targets and treatment efficacy monitoring. Furthermore, in the last 2 years, the SARS-CoV-2 (severe acute respiratory syndrome-coronavirus) pandemic has had an important impact on health system, leading us to update approaches on how to manage hypersensitivity reactions to drugs used for its treatment and on COVID-19 (Coronavirus disease) vaccines used for its prevention. This article reviews recent advances in these 3 areas regarding drug hypersensitivity: in vitro tools for drug hypersensitivity diagnosis, recently identified biomarkers that could guide clinical decision making and management of hypersensitivity reactions to drugs and vaccines used for COVID-19.
Pre-exposure prophylaxis with tixagevimab and cilgavimab (Evusheld) for COVID-19 among 1112 severely immunocompromised patients
Authors: Yann Nguyen, Adrien Flahault, Nathalie Chavarot, Cléa Melenotte, Morgane Cheminant, Paul Deschamps, Nicolas Carlier, Emmanuel Lafont, Marion Thomas, Edouard Flamarion, David Lebeaux, Caroline Charlier, Anne Rachline, Corinne Guérin, Robert Ratiney, Justine Touchard, Hélène Péré, Flore Rozenberg, Fanny Lanternier, Jean-Benoît Arlet, Jérôme Avouac, Véronique Boussaud, Romain Guillemain, Marguerite Vignon, Eric Thervet, Anne Scemla, Laurence Weiss, Luc Mouthon
Journal: Clinical Microbiology and Infection (2022)
Editorial Board and Contents
Authors: Kusumika Mukherjee, Paige Shaklee, Fred Kop, Patrick Scheffmann, Michelle Arkin, Jacqueline Crawley, A Cuello, Laszlo Hunyady, Magnus Ingelman-Sundberg, Allan Kalueff, Terry Kenakin, Brian Kobilka, Michel Lazdunski, Christian Lüscher, Fiona Marshall, Jacopo Meldolesi, Wouter Moolenaar, Ruth Nussinov, Clive Page, Leonardo Pardo, Harald Sitte, Roger Summers, Rachel Tyndale, Ming-Wei Wang, Steven Watson, Stephen Waxman
Journal: Trends in Pharmacological Sciences (2018)
Editorial Board and Contents
Authors: Moran Furman, Paige Shaklee, Fred Kop, Patrick Scheffmann, Silvia Arber, Anders Björklund, J Paul Bolam, Sarah Bottjer, Rui Costa, Ann Marie, Craig Barry, J Dickson, Chris Doe, Craig Garner, Yukiko Goda, Kenneth Harris, Nancy Ip, Meyer Jackson, Maria Karayiorgou, Robert Malenka, Mark Mattson, Freda Miller, Richard Morris, Maiken Nedergaard, Eric Nestler, Anna Roe, Hitoshi Sakano, Greg Stuart, Marc Tessier-Lavigne, Chris Walsh
Journal: Trends in Neurosciences (2018)
Editorial Board and Contents
Authors: Susanne Brink, Caeul Lim, Paige Shaklee, Margriet Ten Napel, Patrick Scheffmann, Göran Arnqvist, Spencer Barrett, Michael Bell, Brendan Bohannan, Ragan Callaway, Stephen Carpenter, James Clark, Paul Dayton, Rodolfo Dirzo, Andrew Dobson, Michael Donoghue, Douglas Irwin, Yoh Iwasa, Stephen Jackson, Christian Köner, William Laurance, Georgina Mace, Harold Mooney, Craig Moritz, Randolph Nesse, Sarah Otto, Svante Pääbo, Linda Partridge, David Penny, Andrew Read, Daven Presgraves, Benjamin Sheldon, Christine Simon, Boris Worm
Journal: Trends in Ecology & Evolution (2018)
Granular B lymphoblastic leukemia
Authors: Biswadip Hazarika, Barbara J. Bain
Journal: American Journal of Hematology (2022)

A 13-year-old Indian boy presented with extreme lethargy and weakness. On examination, there was no hepatosplenomegaly or lymphadenopathy. His blood count showed a white cell count of 18.8 × 109/L, hemoglobin concentration 107 g/L, and platelet count 70 × 109/L. Examination of a blood film led to suspicion of granular lymphoblastic leukemia. There were 60% blast cells with a moderately high nucleocytoplasmic ratio, delicate chromatin, and 1–3 nucleoli. Many of the blast cells contained prominent azurophilic cytoplasmic granules. There were no Auer rods and granulocyte morphology was normal. The suspected lineage was confirmed by flow cytometric immunophenotyping which showed the blast cells to express CD45 (weak), CD34, CD10, CD19, CD20, cytoplasmic(c) CD79a, CD33, and HLA-DR. There was no expression of myeloperoxidase, cCD3, CD7, CD13, CD64, or CD117. Cytogenetic analysis showed a normal male karyotype. Reverse transcriptase for BCR::ABL1 did not detect p210, p190, or p230 transcripts. Granular acute lymphoblastic leukemia (ALL) is uncommon. Making a distinction from acute myeloid and mixed phenotype, acute leukemia is important and requires myeloperoxidase cytochemistry or immunophenotyping. Most cases are pro-B or common ALL but T-lineage cases have also been reported. In addition to B-lineage-specific markers, there can be aberrant expression of CD131 or CD33.2, 3 There is no specific cytogenetic association and the prognostic significance, if any, is uncertain. The authors declare no conflict of interest
<i>Transferrin receptor 2 (Tfr2)</i> genetic deletion makes transfusion‐independent a murine model of transfusion‐dependent β‐thalassemia
Authors: Simona Maria Di Modica, Emanuele Tanzi, Violante Olivari, Maria Rosa Lidonnici, Mariateresa Pettinato, Alessia Pagani, Francesca Tiboni, Valeria Furiosi, Laura Silvestri, Giuliana Ferrari, Stefano Rivella, Antonella Nai
Journal: American Journal of Hematology (2022)

β-thalassemia is a genetic disorder caused by mutations in the β-globin gene, and characterized by anemia, ineffective erythropoiesis and iron overload. Patients affected by the most severe transfusion-dependent form of the disease (TDT) require lifelong blood transfusions and iron chelation therapy, a symptomatic treatment associated with several complications. Other therapeutic opportunities are available, but none is fully effective and/or applicable to all patients, calling for the identification of novel strategies. Transferrin receptor 2 (TFR2) balances red blood cells production according to iron availability, being an activator of the iron-regulatory hormone hepcidin in the liver and a modulator of erythropoietin signaling in erythroid cells. Selective Tfr2 deletion in the BM improves anemia and iron-overload in non-TDT mice, both as a monotherapy and, even more strikingly, in combination with iron-restricting approaches. However, whether Tfr2 targeting might represent a therapeutic option for TDT has never been investigated so far. Here, we prove that BM Tfr2 deletion improves anemia, erythrocytes morphology and ineffective erythropoiesis in the Hbbth1/th2 murine model of TDT. This effect is associated with a decrease in the expression of α-globin, which partially corrects the unbalance with β-globin chains and limits the precipitation of misfolded hemoglobin, and with a decrease in the activation of unfolded protein response. Remarkably, BM Tfr2 deletion is also sufficient to avoid long-term blood transfusions required for survival of Hbbth1/th2 animals, preventing mortality due to chronic anemia and reducing transfusion-associated complications, such as progressive iron-loading. Altogether, TFR2 targeting might represent a promising therapeutic option also for TDT.
Inflammatory pathways in COVID‐19: Mechanism and therapeutic interventions
Authors: Yujie Jiang, Tingmei Zhao, Xueyan Zhou, Yu Xiang, Pedro Gutierrez‐Castrellon, Xuelei Ma
Journal: MedComm (2022)

The 2019 coronavirus disease (COVID-19) pandemic has become a global crisis. In the immunopathogenesis of COVID-19, SARS-CoV-2 infection induces an excessive inflammatory response in patients, causing an inflammatory cytokine storm in severe cases. Cytokine storm leads to acute respiratory distress syndrome, pulmonary and other multiorgan failure, which is an important cause of COVID-19 progression and even death. Among them, activation of inflammatory pathways is a major factor in generating cytokine storms and causing dysregulated immune responses, which is closely related to the severity of viral infection. Therefore, elucidation of the inflammatory signaling pathway of SARS-CoV-2 is important in providing otential therapeutic targets and treatment strategies against COVID-19. Here, we discuss the major inflammatory pathways in the pathogenesis of COVID-19, including induction, function, and downstream signaling, as well as existing and potential interventions targeting these cytokines or related signaling pathways. We believe that a comprehensive understanding of the regulatory pathways of COVID-19 immune dysregulation and inflammation will help develop better clinical therapy strategies to effectively control inflammatory diseases, such as COVID-19.
Forthcoming Meetings
Journal: Neuro-Oncology (2022)

Journal Article Forthcoming Meetings Get access Neuro-Oncology, Volume 24, Issue 8, August 2022, Page 1405, https://doi.org/10.1093/neuonc/noac164 Published: 01 August 2022 Article history Corrected and typeset: 01 August 2022 Published: 01 August 2022
Editorial Board and Contents
Authors: Caryn Navarro, Danielle Loughlin, Paige Shaklee, Yvonne Philippo, Patrick Scheffmann, Erik Andersen, Kirsten Bomblies, Martha Bulyk, Ling Chen, Andy Clark, Sue Clark, Susan Gasser, David Goldstein, Leonard Guarente, Yoshihide Hayashizaki, Steven Henikoff, Chris Hittinger, Laurence Hurst, Aldons Lusis, Angela Nieto, Chris Ponting, Claudio Scazzocchio, Bob Schmitz, Nicole Soranzo, Trisha Wittkopp, Joanna Wysocka
Journal: Trends in Genetics (2018)
Minimal invasiveness in the alveolar ridge preservation, with or without concomitant implant placement
Authors: Maurício G. Araújo, Markus B. Hürzeler, Debora R. Dias, Flavia Matarazzo
Journal: Periodontology 2000 (2022)

Abstract The aim of this systematic review was to evaluate the benefit of ridge preservation (RP) with minimally invasive (MI) approaches with or without concomitant implant placement on morbidity, esthetics, and patient‐related outcomes. Three Internet sources were used to search for appropriate papers. The search strategy was designed to include any clinical study published on RP with MI approaches such as flapless surgery, socket shield and socket sealing techniques and, use of biological agents. Characteristics of the individual studies, regarding methodological aspects, quantitative and qualitative data were extracted. The potential risk of bias was estimated, and the acquired evidence was graded. Independent screening of 860 reports resulted in 26 included original articles. Nine publications evaluated MI approaches for RP without concomitant implant placement. Eleven studies evaluated interventions for RP with immediate implant placement (IIP). Six studies compared RP with IIP vs RP without IIP. This systematic review found that MI approaches in most of the studies failed to improve clinical variables regarding morbidity, esthetics, and patient‐related outcomes. Based on the limited number of studies analyzed and the methodological discrepancies observed, it is not possible to confirm that MI approaches promote a significant benefit when applied to RP procedures.
Functional 2D Iron‐Based Nanosheets for Synergistic Immunotherapy, Phototherapy, and Chemotherapy of Tumor
Authors: Xingbo Wang, Yan Cheng, Xiaoqing Han, Jiao Yan, Yunyun Wu, Panpan Song, Yanjing Wang, Xi Li, Haiyuan Zhang
Journal: Advanced Healthcare Materials (2022)

Abstract Immunotherapy efficacy has been limited by tumor‐associated macrophages (TAMs), which are the most abundant immune regulatory cells infiltrating around tumor tissues. The repolarization of pro‐tumor M2 TAMs to anti‐tumor M1 TAMs is a very promising immunotherapeutic strategy for cancer therapy. In this manuscript, multifunctional 2D iron‐based nanosheets (FeNSs) are synthesized via a simple hydrothermal method for the first time, which not only possess photothermal and photodynamic properties, but also can repolarize TAMs from M2 to M1. After modifying with polyethylene glycol and loading with bioreductive prodrug banoxantrone (AQ4N), abbreviated as AP FeNSs, it can effectively repolarize TAMs from M2 to M1 and deliver AQ4N to tumor microenvironment (TME). Moreover, the repolarized M1 TAMs overexpress inducible nitric oxide synthase, which can convert nontoxic AQ4N to cytotoxic AQ4 under hypoxic TME, enabling immunomodulation‐activated chemotherapy. A series of in vitro and in vivo results corroborate that AP FeNSs effectively exert photothermal and photodynamic effects and repolarize M2 TAMs to M1 TAMs, releasing inflammatory factors and activating the chemotherapeutic effect, thereby realizing synergistic tumor therapy.
Differential richness inference for 16S rRNA marker gene surveys
Authors: M. Senthil Kumar, Eric V. Slud, Christine Hehnly, Lijun Zhang, James Broach, Rafael A. Irizarry, Steven J. Schiff, Joseph N. Paulson
Journal: Genome biology (2022)

Individual and environmental health outcomes are frequently linked to changes in the diversity of associated microbial communities. Thus, deriving health indicators based on microbiome diversity measures is essential. While microbiome data generated using high-throughput 16S rRNA marker gene surveys are appealing for this purpose, 16S surveys also generate a plethora of spurious microbial taxa.
Performance measures for colonoscopy in inflammatory bowel disease patients: European Society of Gastrointestinal Endoscopy (ESGE) Quality Improvement Initiative
Authors: Evelien Dekker, Karlijn J. Nass, Marietta Iacucci, Alberto Murino, João Sabino, Marek Bugajski, Cristina Carretero, George Cortas, Edward J. Despott, James E. East, Michal F. Kaminski, John Gásdal Karstensen, Martin Keuchel, Mark Löwenberg, Ashraf Monged, Olga M. Nardone, Helmut Neumann, Mahmoud M. Omar, Maria Pellisé, Laurent Peyrin-Biroulet, Matthew D. Rutter, Raf Bisschops
Journal: Endoscopy (2022)

The European Society of Gastrointestinal Endoscopy (ESGE) presents a short list of performance measures for colonoscopy in inflammatory bowel disease (IBD) patients. Current performance measures for colonoscopy mainly focus on detecting (pre)malignant lesions. However, these performance measures are not relevant for all colonoscopy indications in IBD patients. Therefore, our aim was to provide endoscopy services across Europe and other interested countries with a tool for quality monitoring and improvement in IBD colonoscopy. Eight key performance measures and one minor performance measure were recommended for measurement and evaluation in daily endoscopy practice.
Minimal invasiveness in the transcrestal elevation of the maxillary sinus floor: A systematic review
Authors: Roberto Farina, Chiara Franzini, Leonardo Trombelli, Anna Simonelli
Journal: Periodontology 2000 (2022)

In the attempt to reduce the invasiveness of a transcrestal sinus floor elevation procedure, different aspects must be considered; that is, the minimization of intra- and postsurgery morbidity, the reduction of treatment time, and the simplification/elimination of the reconstructive technology. Within this context, a systematic literature search was performed for controlled clinical trials evaluating the impact of one or more of these aspects on transcrestal sinus floor elevation invasiveness. Nineteen articles (15 studies) were included. Overall, the results confirmed that transcrestal sinus floor elevation is a minimally invasive and effective option for bone augmentation in the edentulous, atrophic posterior maxilla. By using powered instruments rather than manual osteotomes and hand mallet, the invasiveness of transcrestal sinus floor elevation can be further reduced without affecting its clinical effectiveness. To impact effectively on morbidity, the key elements to consider when selecting instruments for transcrestal sinus floor elevation are (a) their availability as a standardized sequence, to be adapted on predetermined residual bone height, and (b) the possibility to control pressure (eg, with screwable osteotomes) and/or instrument excursion (eg, with stop devices) to fracture the maxillary sinus floor. Among powered instruments, a standardized sequence of drills incorporating a trephine drill seem to be particularly indicated, due to reduced chair time, high tolerability for the patient, and the possibility to isolate a bone core to implement histomorphometric outcomes. At molar extraction sites with an interradicular septum characterized by a height of at least 4 mm, immediate transcrestal sinus floor elevation and implant placement can be considered a valid option to shorten treatment time.
A novel endoscopic suture strategy using barbed string
Authors: Tianyu Zhang, Dong Wang
Journal: Endoscopy (2022)

Gastrointestinal perforation is a common complication of endoscopic therapy, especially with some novel approaches such as endoscopic submucosal dissection (ESD) [1], that can lead to serious or even life-threatening outcomes if not handled properly. With the rapid development of endoscopic techniques, various endoscopic suture methods for closing the defect have been reported [2] [3] [4]. However, most of the closure devices are expensive and require complicated manipulation. Consequently, it is still difficult to handle endoscopic perforation effectively in clinical practice [5]. We report here a novel suturing strategy using barbed string that is easy to master and is cheaper than other available suturing methods.
Resection of subepithelial lesions by a novel technique: “Band endoscopic full-thickness resection”
Authors: Hira Cheema, Saikiran Raghavapuram, Iman Boston, Cem Cengiz, Jiannis Anastasiou, Sumant Inamdar, Benjamin Tharian
Journal: Endoscopy (2022)

Endoscopic full-thickness resection (EFTR) using a full-thickness resection device is a Food and Drug Administration (FDA)-approved minimally invasive technique for resecting subepithelial tumors of the gastrointestinal (GI) tract [1] [2] [3] [4] [5]. Grasping and pulling the entire lesion into the cap is a technical challenge, as the mucosa tears off despite cautious traction. We describe a novel technique deploying a band and subsequently grasping and resecting the lesion en bloc. The "pseudo-polyp" reduces the tension on the mucosa as the subepithelial tumor anchored by the band is partially held onto by the grasper, minimizing the shearing forces between the mucosa and the underlying tumor.
Endoscopy International Open – recently published
Journal: Endoscopy (2018)

Comment on: Endoscopic submucosal dissection for rectal neoplasia extending to the dentate line: European experienceEndosc Int Open 2018; 06(11): E1355-E1362DOI: 10.1055/a-0749-8735 Comment on: Green epithelium revealed by narrow-band imaging (NBI): a feature for practical assessment of extent of gastric cancer after H. pylori eradicationEndosc Int Open 2018; 06(11): E1289-E1295DOI: 10.1055/a-0746-3449 Comment on: Peroral cholangioscopy by SpyGlass DS versus CHF-B260 for evaluation of the lateral spread of extrahepatic cholangiocarcinomaEndosc Int Open 2018; 06(11): E1349-E1354DOI: 10.1055/a-0743-5283
Lincoln: A Psycho-Biography.
Journal: JAMA (1933)

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